start-ver=1.4 cd-journal=joma no-vol=452 cd-vols= no-issue= article-no= start-page=104 end-page=113 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190815 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fgf- and Bmp-signaling regulate gill regeneration in Ambystoma mexicanum en-subtitle= kn-subtitle= en-abstract= kn-abstract= Gill regeneration has not been well studied compared to regeneration of other appendages, such as limb and tail regeneration. Here, we focused on axolotl gill regeneration and found that Fgf- and Bmp-signaling are involved in their gill regeneration mechanism. Axolotls have three pairs of gill rami, and each gill ramus has multiple gill filaments. The gills consist of mesenchyme rich in extracellular matrix and epidermis. The gill nerves are supplied from the trigeminal ganglia located in the head. Denervation resulted in no gill regeneration responses. Nerves and gills express Bmp and Fgf genes, and treating animals with Fgf- and Bmp-signaling inhibitors results in phenotypes similar to those seen in denervated gills. Inducing an accessory appendage is a standard assay in amphibian regeneration research. In our study, an accessory gill could be induced by lateral wounding, suggesting that thin axon fibers and mesenchymal Fgfs and Bmps contributed to the induction of the accessory structure. Such accessory gill induction was inhibited by the denervation. Exogenous Fgf2+Fgf8+Bmp7, which have been determined to function as a regeneration inducer in urodele amphibians, could compensate for the effects denervation has on accessory blastema formation. Our findings suggest that regeneration of appendages in axolotls is regulated by common Fgf- and Bmp-signaling cascades. en-copyright= kn-copyright= en-aut-name=Saito Nanami en-aut-sei=Saito en-aut-mei= Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Nishimura Koki en-aut-sei=Nishimura en-aut-mei= Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Makanae Aki en-aut-sei=Makanae en-aut-mei= Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University, Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=2 en-affil=Okayama University, Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=3 en-affil=Okayama University, Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=4 en-affil=Okayama University, Research Core for Interdisciplinary Sciences (RCIS) kn-affil= en-keyword=Blastema induction kn-keyword=Blastema induction en-keyword= Bmp kn-keyword= Bmp en-keyword=Fgf kn-keyword=Fgf en-keyword=Gill regeneration kn-keyword=Gill regeneration en-keyword=Nerve kn-keyword=Nerve en-keyword=Organ regeneration kn-keyword=Organ regeneration END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=9323 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neural regulation in tooth regeneration of Ambystoma mexicanum en-subtitle= kn-subtitle= en-abstract= kn-abstract=The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. en-copyright= kn-copyright= en-aut-name=MakanaeAki en-aut-sei=Makanae en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TajikaYuki en-aut-sei=Tajika en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraKoki en-aut-sei=Nishimura en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoNanami en-aut-sei=Saito en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaJun-Ichi en-aut-sei=Tanaka en-aut-mei=Jun-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=2 en-affil=Gunma University, Department of Anatomy, Graduate School of Medicine kn-affil= affil-num=3 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=4 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=5 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=6 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= en-keyword=Cell proliferation kn-keyword=Cell proliferation en-keyword=Differentiation kn-keyword=Differentiation en-keyword=Morphogenesis kn-keyword=Morphogenesis END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=7 article-no= start-page=104524 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lattice-patterned collagen fibers and their dynamics in axolotl skin regeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=The morphology of collagen-producing cells and the structure of produced collagen in the dermis have not been well-described. This lack of insights has been a serious obstacle in the evaluation of skin regeneration. We succeeded in visualizing collagen-producing cells and produced collagen using the axolotl skin, which is highly transparent. The visualized dermal collagen had a lattice-like structure. The collagen-producing fibroblasts consistently possessed the lattice-patterned filopodia along with the lattice-patterned collagen network. The dynamics of this lattice-like structure were also verified in the skin regeneration process of axolotls, and it was found that the correct lattice-like structure was not reorganized after simple skin wounding but was reorganized in the presence of nerves. These findings are not only fundamental insights in dermatology but also valuable insights into the mechanism of skin regeneration. en-copyright= kn-copyright= en-aut-name=KashimotoRena en-aut-sei=Kashimoto en-aut-mei=Rena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurukawaSaya en-aut-sei=Furukawa en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoSakiya en-aut-sei=Yamamoto en-aut-mei=Sakiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KameiYasuhiro en-aut-sei=Kamei en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoJoe en-aut-sei=Sakamoto en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NonakaShigenori en-aut-sei=Nonaka en-aut-mei=Shigenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeTomonobu M. en-aut-sei=Watanabe en-aut-mei=Tomonobu M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biological Sciences, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Biological Sciences, Faculty of Science, Okayama University kn-affil= affil-num=4 en-affil=National Institute for Basic Biology (NIBB), National Institutes for Natural Sciences kn-affil= affil-num=5 en-affil=National Institute for Basic Biology (NIBB), National Institutes for Natural Sciences kn-affil= affil-num=6 en-affil=National Institute for Basic Biology (NIBB), National Institutes for Natural Sciences kn-affil= affil-num=7 en-affil=Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research (BDR) kn-affil= affil-num=8 en-affil=Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Research Core for Interdisciplinary Sciences (RCIS), Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=6 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Urodele amphibians, Pleurodeles waltl and Ambystoma mexicanum, have organ-level regeneration capability, such as limb regeneration. Multipotent cells are induced by an endogenous mechanism in amphibian limb regeneration. It is well known that dermal fibroblasts receive regenerative signals and turn into multipotent cells, called blastema cells. However, the induction mechanism of the blastema cells from matured dermal cells was unknown. We previously found that BMP2, FGF2, and FGF8 (B2FF) could play sufficient roles in blastema induction in urodele amphibians. Here, we show that B2FF treatment can induce dermis-derived cells that can participate in multiple cell lineage in limb regeneration. We first established a newt dermis-derived cell line and confirmed that B2FF treatment on the newt cells provided plasticity in cellular differentiation in limb regeneration. To clarify the factors that can provide the plasticity in differentiation, we performed the interspecies comparative analysis between newt cells and mouse cells and found the Pde4b gene was upregulated by B2FF treatment only in the newt cells. Blocking PDE4B signaling by a chemical PDE4 inhibitor suppressed dermis-to-cartilage transformation and the mosaic knockout animals showed consistent results. Our results are a valuable insight into how dermal fibroblasts acquire multipotency during the early phase of limb regeneration via an endogenous program in amphibian limb regeneration. en-copyright= kn-copyright= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KashimotoRena en-aut-sei=Kashimoto en-aut-mei=Rena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiAyaka en-aut-sei=Ohashi en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FurukawaSaya en-aut-sei=Furukawa en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoSakiya en-aut-sei=Yamamoto en-aut-mei=Sakiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueTakeshi en-aut-sei=Inoue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayashiToshinori en-aut-sei=Hayashi en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AgataKiyokazu en-aut-sei=Agata en-aut-mei=Kiyokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Research Core for Interdisciplinary Sciences (RCIS), Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Envi�ronmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Envi�ronmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Science, Department of Biological Sciences, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Science, Department of Biological Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Adaptation Physiology, Faculty of Medicine, Tottori University kn-affil= affil-num=7 en-affil=Amphibian Research Center, Hiroshima University kn-affil= affil-num=8 en-affil=Laboratory of Regeneration Biology, National Institute for Basic Biology kn-affil= en-keyword=Pde4b kn-keyword=Pde4b en-keyword=Limb regeneration kn-keyword=Limb regeneration en-keyword=Pleurodels waltl kn-keyword=Pleurodels waltl en-keyword=Ambystoma mexicanum kn-keyword=Ambystoma mexicanum en-keyword=Dedifferentiation kn-keyword=Dedifferentiation en-keyword=Reprogramming kn-keyword=Reprogramming END